Postoperative radiation therapy for patients at high-risk of recurrence after radical prostatectomy: does timing matter?

OBJECTIVE: To evaluate among radical prostatectomy (RP) patients at high-risk of recurrence whether the timing of postoperative radiation therapy (RT) (adjuvant, early salvage with detectable post-RP prostate-specific antigen [PSA], or 'late' salvage with a PSA level of >1.0 ng/mL) is significantly associated with overall survival (OS), prostate-cancer specific survival or metastasis-free survival, in a longitudinal cohort. PATIENTS AND METHODS: Of 6 176 RP patients in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), 305 patients with high-risk pathological features (margin positivity, Gleason score 8-10, or pT3-4) who underwent postoperative RT were examined, either in the adjuvant (≤6 months after RP with undetectable PSA levels, 76 patients) or salvage setting (>6 months after RP or pre-RT PSA level of >0.1 ng/mL, 229 patients). Early (PSA level of ≤1.0 ng/mL, 180 patients) or late salvage RT (PSA level >1.0 ng/mL, 49 patients) was based on post-RP, pre-RT PSA level. Multivariable Cox regression examined associations with all-cause mortality and prostate cancer-specific mortality and/or metastases (PCSMM). RESULTS: After a median of 74 months after RP, 65 men had died (with 37 events of PCSMM). Adjuvant and salvage RT patients had comparable high-risk features. Compared with adjuvant, salvage RT (early or late) had an increased association with all-cause mortality (hazard ratio [HR] 2.7, P = 0.018) and with PCSMM (HR 4.0, P = 0.015). PCSMM-free survival differed by further stratification of timing, with 10-year estimates of 88%, 84%, and 71% for adjuvant, early salvage, and late salvage RT, respectively (P = 0.026). For PCSMM-free survival and OS, compared with adjuvant RT, late salvage RT had statistically significantly increased risk; however, early salvage RT did not. CONCLUSION: This analysis suggests that patients who underwent early salvage RT with PSA levels of <1.0 ng/mL may have comparable metastasis-free survival and OS compared with adjuvant RT; however, late salvage RT with a PSA level of >1.0 ng/mL is associated with worse clinical outcomes.

Impact of national guidelines on brachytherapy monotherapy practice patterns for prostate cancer.

BACKGROUND: In 1999 and 2000, 2 national guidelines recommended brachytherapy monotherapy (BT) primarily for treatment of low-risk prostate cancer but not high-risk prostate cancer. This study examined rates of BT use before and after publication of these guidelines, as compared with 4 other treatment options. METHODS: From 1990 to 2011, 8128 men with localized prostate cancer (≤ T3cN0M0) were treated definitively within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry with 1 of 5 primary treatments: BT, external beam radiotherapy (EBRT), EBRT with androgen deprivation therapy, EBRT+BT, or radical prostatectomy. Men were categorized into low-, intermediate-, and high-risk groups based on the guidelines' risk-group definitions. Within each risk group, logistic regression was used to estimate odds ratios (OR) comparing BT with other treatment options between the 1990-1998 and 1999-2011 periods, adjusting for age, disease characteristics, and clinic type. RESULTS: In total, 1117 men received BT alone for low- (n = 658), intermediate- (n = 244), or high-risk disease (n = 215). BT comprised 6.1% of all treatments in 1990-1998 versus 16.6% in 1999-2011 (P < .01). The odds of BT use remained increased after adjusting for potential confounders (OR = 3.06; P < .001) and was seen among low- (OR = 4.52; P < .001), intermediate- (OR = 2.67; P < .001), and even high-risk groups (OR = 2.11; P < .001). CONCLUSIONS: National guidelines did not appear to influence practice patterns, as BT monotherapy use increased relative to other treatments from the 1990-1998 to 1999-2011 periods in unfavorable risk groups including men with high-risk prostate cancer.

Feasibility, Acceptability, and Behavioral Outcomes from a Technology-enhanced Behavioral Change Intervention (Prostate 8): A Pilot Randomized Controlled Trial in Men with Prostate Cancer.

BACKGROUND: Increasing evidence suggests that lifestyle factors may decrease the risk of prostate cancer progression. Lifestyle guidelines and tools may support lifestyle modification after diagnosis. OBJECTIVE: To determine the feasibility and acceptability of a digital lifestyle intervention among men with prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: A 12-wk pilot randomized controlled trial among 76 men with clinical stage T1-T3a prostate cancer. Eligibility included Internet access, no contraindications to aerobic exercise, and engaging in four or fewer of eight targeted behaviors at baseline. INTERVENTION: Website, Fitbit One, and text messaging to facilitate adoption of eight behaviors: vigorous activity, smoking cessation, and six diet improvements. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Our primary outcomes were feasibility and acceptability based on recruitment and user data, and surveys, respectively. Secondarily, we evaluated the change in eight lifestyle behaviors, and also objective physical activity. Each factor was assigned one point, for an overall "P8 score" (range 0-8). Analysis of covariance (ANCOVA) was conducted. Exploratory outcomes included quality of life, anthropometrics, and circulating biomarkers after 12wk, and behaviors after 1yr. RESULTS AND LIMITATIONS: At baseline, men in both arms met a median of three targeted behaviors. Sixty-four men (n=32 per arm) completed the study; 88% completed 12-wk assessments (intervention, 94%; control, 82%). Intervention participants wore their Fitbits a median of 82d (interquartile range [IQR]: 72-83), replied to a median of 71% of text messages (IQR: 57-89%), and visited the website a median of 3d (IQR: 2-5) over 12wk. Median (IQR) absolute changes in the P8 score from baseline to 12wk were 2 (1, 3) for the intervention and 0 (-1, 1) for the control arm. The estimated mean score of the intervention arm was 1.5 (95% confidence interval: 0.7, 2.3) higher than that of the control arm at 12wk (ANCOVA p<0.001). Changes were driven by diet rather than exercise. Limitations include self-reported diet and exercise data. CONCLUSIONS: Overall, in this novel pilot trial, the intervention was feasible and acceptable to men with prostate cancer. Next steps include improving the intervention to better meet individuals' needs and focusing on increasing physical activity in men not meeting nationally recommended physical activity levels. PATIENT SUMMARY: Tailored print materials combined with technology integration, including the use of a website, text messaging, and physical activity trackers, helped men with prostate cancer adopt healthy lifestyle habits, in particular recommended dietary changes, in the Prostate 8 pilot trial.

Impact of ethnicity on primary treatment choice and mortality in men with prostate cancer: data from CaPSURE.

PURPOSE Men diagnosed with prostate cancer have multiple options available for treatment. Previous reports have indicated a trend of differing modalities of treatment chosen by African American and white men. We investigated the role of ethnicity in primary treatment choice and how this affected overall and cancer-specific mortality. METHODS By utilizing data abstracted from Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), patients were compared by ethnicity, primary treatment, number of comorbidities, risk level according to modified D'Amico criteria, age, highest educational level attained, type of insurance, treatment facility, and perception of general health. Multinomial logistic regression analysis was performed to determine the effect of the tested variables on primary treatment and mortality. Results African American men were more likely to receive nonsurgical therapy than white men with equivalent disease characteristics. Whites were 48% less likely than African Americans to receive androgen deprivation therapy (ADT) compared with surgery (P = .02) and were 25% less likely than African Americans to receive radiation therapy compared with surgery (P = .08). Whites with low-risk disease were 71% less likely to receive ADT than African American men with similar disease (P = .01). Adjusted overall and prostate cancer-specific mortality were not significantly different between whites and African Americans (hazard ratios, 0.73 and 0.37, respectively). Risk level, type of treatment, and type of insurance had the strongest effects on risk of mortality. CONCLUSION There is a statistically significant difference in primary treatment for prostate cancer between African American and white men with similar risk profiles. Additional research on the influence of patient/physician education and perception and the role that socioeconomic factors play in mortality from prostate cancer may be areas of focus for public health initiatives.

Impact of radical prostatectomy positive surgical margins on fear of cancer recurrence: results from CaPSURE.

PURPOSE: Fear of cancer recurrence (FCR) is a significant source of distress in men with prostate cancer and could affect clinical decision-making, especially in those with positive margins following radical prostatectomy (RP). We examined the influence of positive surgical margin status on fear of cancer recurrence in men undergoing radical prostatectomy. METHODS: Five hundred eight-four men underwent RP from 1999 to 2002 in CaPSURE, a prospective, longitudinal, national cohort. All men had both baseline and follow-up assessment of FCR using a validated Kornblith scale. Statistical analysis included chi(2) test, Wald test, and linear as well as repeated measures ANOVA mixed model. RESULTS: One hundred sixty (27%) men had positive surgical margins. Baseline FCR and clinical variables did not differ based on margin status. Men with positive margins experienced greater FCR after RP than negative margins (OR, 1.94, 95% CI, 1.22-3.07). Men who had received adjuvant therapy experienced greater FCR (OR, 2.78, 95% CI, 1.21-6.39). Repeated measures analysis showed greater FCR over time (14-month mean follow-up, range 2-31 months) for positive vs. negative margins (P = 0.02). This difference in fear widened over time. There were no significant differences in health-related quality of life scores based on margin status. CONCLUSION: Positive surgical margin status is associated with greater fear of cancer recurrence, a difference not alleviated by adjuvant therapy use. Men with positive margins remain more fearful over the course of several years compared with those with negative margins. Clinicians should be aware of the potential stressful impact of positive surgical margins.